Parasitic Central Nervous System Infections in Immunocompromised Hosts: Clarification of Malaria Diagnosis

To the Editor—We would like to compliment Walker et al. [1] on their informative review article on CNS parasitic infections in immuncompromised hosts. However, there is a statement and a table regarding the diagnosis of malaria using serological tests and rapid malaria tests that is misleading and deserves clarification. This is particularly important, because the submission package for the first rapid malaria test that may be approved in the United States is nearing completion. Walker et al. state that the “[s]erological tests (ParaSight-F and Immunochromotographic Malaria P[lasmodium] falciparum test) are available, but false-positive test results are common” [1, p. 118]. Table 3 on page 117 of their article makes a similar statement and also indicates that the specimen type for the ParaSight-F (Becton Dickinson) and Immunochromotographic tests is a serum sample. It is important to distinguish serological tests and antigen detection tests and the appropriate specimen type for these assays. Serological assays (for the detection of anti-malarial IgG and IgM in patient serum) have limited clinical utility for the diagnosis of malaria [2]. Most individuals who have resided in areas of moderate or high endemicity for malaria will demonstrate a persistent antibody response. On the other hand, several rapid malaria tests based on the detection of malaria antigens in whole blood samples, such as parasite histidine-rich protein II, aldolase, and lactate dehydrogenase, are available on the global market (however, as far as we know, ParaSight-F is no longer manufactured). These newer-generation assays display high sensitivity and specificity for acute clinical P. falciparum infections, with more variable results for infection due to non-falciparum species of Plasmodium [3–6]. A pivotal clinical trial evaluating the performance of the NOW ICT (Binax) rapid antigen test in >4000 patients was recently presented at the American Society of Tropical Medicine and Hygiene Annual Conference in Washington, D.C., in December 2005 by the US Army [7]. Overall sensitivity and specificity were 95% and 94%, respectively, for P. falciparum infection and 69% and 99%, respectively, for Plasmodium vivax infection. For parasite counts of >5000 parasites/µ L, sensitivity was >99% for P. falciparum infection and 94% for P. vivax infection. In addition, the authors state “false-positive test results are common” [1, p. 117]. In many instances, “false-positives” are seen because the rapid test is more sensitive than routine microscopic examination (with histidine-rich protein II–based tests) or because antigenemia persists for a few days after clearance of parasites. True false-positive test results (i.e., instances in which the rapid test result is positive, but the patient does not have malaria) are much less common in field use. Occasional false-positive results have been seen in patients with a positive rheumatoid factor with some test kits [8]. It is important for infectious disease specialists to understand the appropriate sample type, properties, clinical utility, limitations, and performance characteristics of diagnostic tests for this important disease.

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